Dexamethasone for treating SARS-CoV-2 infection: a systematic review and meta-analysis

ABSTRACT BACKGROUND: Considering the disruptions imposed by lockdowns and social distancing recommendations, coupled with overwhelmed healthcare systems, researchers worldwide have been exploring drug repositioning strategies for treating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). OBJECTIVE: To compile results from randomized clinical trials on the effect of dexamethasone, compared with standard treatment for management of SARS-CoV-2. DESIGN AND SETTING: We conducted a systematic review and meta-analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in a Brazilian public university. METHODS: We sought to compile data from 6724 hospitalized patients with confirmed or suspected SARS-CoV-2 infection. RESULTS: Treatment with dexamethasone significantly reduced mortality within 28 days (risk ratio, RR: 0.89; 95% confidence interval, CI: 0.82-0.97). Dexamethasone use was linked with being discharged alive within 28 days (odds ratio, OR: 1.20; 95% CI: 1.07-1.33). CONCLUSIONS: This study suggests that dexamethasone may significantly improve the outcome among hospitalized patients with SARS-CoV-2 infection and associated severe respiratory complications. ­Further studies need to consider both dose-dependent administration and outcomes in early and later stages of the disease. PROSPERO platform: CRD42021229825.

Bone callus formation is highly disrupted by dietary restriction in growing rats sustaining a femoral fracture

Abstract Purpose: To evaluate the effects of food restriction on fracture healing in growing rats. Methods: Sixty-eight male Wistar rats were assigned to two groups: (1) Control and (2) Dietary restriction. After weaning the dietary restricted animals were fed ad libitum for 42 days with 50% of the standard chow ingested by the control group. Subsequently, the animals underwent bone fracture at the diaphysis of the right femur, followed by surgical stabilization of bone fragments. On days 14 and 28 post-fracture, the rats were euthanized, and the fractured femurs were dissected, the callus was analyzed by dual-energy X-ray absorptiometry, micro-computed tomography, histomorphometry, mechanical tests, and gene expression. Results: Dietary restriction decreased body mass gain and resulted in several phenotypic changes at the bone callus (a delay in cell proliferation and differentiation, lower rate of newly formed bone and collagen deposition, reductions in bone callus density and size, decrease in tridimensional callus volume, deterioration in microstructure, and reduction in bone callus strength), together with the downregulated expression of osteoblast-related genes. Conclusion: Dietary restriction had detrimental effects on osseous healing, with a healing delay and a lower quality of bone callus formation.

Undernutrition impairs the quality of growth plate and trabecular and cortical bones in growing rats

Abstract Purpose: To investigate the effects of dietary restriction on the growth plate and long bone tissue in growing rats. Methods: Sixty male Wistar rats were randomly assigned to two groups: Control (Con) and Diet-restricted (Res). After weaning, the Res rats were offered 50% of the chow ingested by the control (ad libitum food intake). The animals were subdivided into two subgroups with follow-ups up to 56 or 70 days. After euthanasia, the growth plate of tibias was analyzed by histomorphometry, micro-computed tomography, and mechanical test. The trabecular and compact bones were evaluated by histomorphometry, dual-energy X-ray absorptiometry, and micro-computed tomography (μCT). Real-time PCR was used to analyze gene expression. Results: Although dietary restriction did not alter gene expression, several phenotypic changes were seen in the growth plate; i.e., decrease in volume, reduction in total area and height, decrease in the area ossified zones, mechanical weakening, reduction in mass of trabecular and cortical bone, lower bone density, deterioration of the trabecular and cortical microarchitecture, and trabeculae with lower collagen deposition. Conclusion: Dietary restriction had severe detrimental effects on the growth plate and trabecular and cortical bone.

Association among H. pylori virulence markers dupA, cagA and vacA in Brazilian patients

Only a few Helicobacter pylori-infected individuals develop severe gastric diseases and virulence factors of H. pylori appear to be involved in such clinical outcomes. Duodenal ulcer promoting gene A (dupA) is a novel virulence factor of Helicobacter pylori that is associated with duodenal ulcer development and reduced risk for gastric carcinoma in some populations. The aims of the present study were to determine the presence of dupA gene and evaluate the association among dupA and other virulence factors including cagA and vacA in Brazilian patients. Gastric biopsies were obtained from 205 dyspeptic patients (100 children and 105 adults). DNA was extracted and analyzed for the presence of H. pylori and its virulence factors using the polymerase chain reaction method.

Association among H. pylori virulence markers dupA, cagA and vacA in Brazilian patients

Only a few Helicobacter pylori-infected individuals develop severe gastric diseases and virulence factors of H. pylori appear to be involved in such clinical outcomes. Duodenal ulcer promoting gene A (dupA) is a novel virulence factor of Helicobacter pylori that is associated with duodenal ulcer development and reduced risk for gastric carcinoma in some populations. The aims of the present study were to determine the presence of dupA gene and evaluate the association among dupA and other virulence factors including cagA and vacA in Brazilian patients. Gastric biopsies were obtained from 205 dyspeptic patients (100 children and 105 adults). DNA was extracted and analyzed for the presence of H. pylori and its virulence factors using the polymerase chain reaction method.

Polimorfismo da Interleucina-8 -251T>A e Helicobacter pylori / Interleukin-8 -251T>A polymorphism and Helicobacter pylori

Introdução: o Helicobacter pylori é um importante patógeno associado ao desenvolvimento de gastrite crônica, úlcera péptica e doenças gástricas. Vários autores relataram que a infiltração de células inflamatórias, incluindo neutrófilos, é um traço da patologia da mucosa gástrica associada com a infecção. Há evidências de que a inflamação está associada à gravidade das lesões gástricas. A interleucina 8 (IL-8), um membro da família das citocinas, é um ativador quimiotático de neutrófilos e linfócitos e tem sido descrito que o aumento dos níveis de IL-8 na mucosa gástrica pode estar associado com a infecção por H.pylori. Objetivos: os objetivos deste trabalho foram (i) caracterizar o polimorfismo da Interleucina-8 -251T>A (ii) e verificar a possível relação entre este polimorfismo e infecção por H.pylori. Métodos: cento e sessenta pacientes sintomáticos (com idade média de 48,7 anos) participaram do estudo: 107 pacientes positivos para H.pylori e 53 negativos, previamente diagnosticados por PCR. Os genótipos da IL-8 -251 T>A foram determinados através da reação em cadeia da polimerase (PCR) e utilização de enzimas de restrição (RFLP). Resultados e Conclusões: nossos resultados indicam que não há associação entre o polimorfismo da IL-8 -251 T>A e a infecção por H.pylori ou pelo gênero dos pacientes.

Background: Helicobacter pylori is an important pathogen associated with the development of chronic gastritis, peptic ulcer disease and gastric disease. Several authors reported that the infiltration of inflammatory cells, including neutrophils is the trace of the pathology of gastric mucosa, associated with the infection. There is high evidence that inflammation is associated with severity of gastric lesions. Interleukin-8 (IL-8), a member of cytokines family, is an activator and chemoattractant of neutrophils and lymphocytes. It has been reported that increased gastric mucosal levels of IL-8 is associated with H. pylori infection. Objective: the objectives of this paper were (i) characterize Interleukin-8 -251T>A polymorphism and (ii) to examine the possible relationship between this polymorphism and the H. pylori infection. Methods: one hundred and sixty patients, (with a mean age 48.7 years) presenting recurrent abdominal pain participated in the study: 107 H. pylori positives and 53 H. pylori negatives previously diagnosed by PCR. IL8 -251T>A genotypes were determined using a polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Results and Conclusions: our findings indicate that there is no association of IL-8 -251T>A with H. pylori-infected patients or gender of these patients and these conclusions were consistent with other reports from different population samples.